External load can alter the energy cost of prolonged exercise

Summary The present study was undertaken to examine the energy cost of prolonged walking while carrying a backpack load. Six trained subjects were tested while walking for 120 min on a treadmill at a speed of 1.25 m · s^–1 and 5% elevation with a well fitted backpack load of 25 and 40 kg alternately. Carrying 40 kg elicited a significantly higher (p<0.01) enery cost than 25 kg. Furthermore, whereas carrying 25 kg resulted in a constant energy cost, 40 kg yielded a highly significant (p<0.05) increase in energy cost over time. The study implies that increase in load causes physical fatigue, once work intensity is higher than 50% maximal work capacity. This is probably due to altered locomotion biomechanics which in turn lead to the increase in energy cost. Finally, the prediction model which estimates energy cost while carrying loads should be used with some caution when applied to heavy loads and long duration of exercise, since it might underestimate the acutal enery cost.     

Treg-Cell Control of a CXCL5-IL-17 Inflammatory Axis Promotes Hair-Follicle-Stem-Cell Differentiation During Skin-Barrier Repair

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CD40 expression by gingival fibroblasts: correlation of phenotype with function

CD40, a member of the tumor necrosis factor-alpha receptor family, is constitutively expressed by cells of hematopoietic and non- hematopoietic origin, including fibroblasts. Signaling through this receptor molecule regulates inflammatory cytokine secretion by many cell types. Based on the recently described cytokine secretory heterogeneity of fibroblast cell subsets, we hypothesized that secretion of inflammatory cytokines by gingival fibroblast cultures may be dictated by the existence of differential proportions of cytokine- secreting subpopulations which express high levels of CD40. After examining a large number of gingival fibroblast (GF) cultures we find that the frequency of IL-6- and IL-8-secreting cells mirrors the frequency of cells expressing high levels of CD40 in these cultures. In addition, we demonstrate a direct functional relationship between CD40 expression and IL-6 or IL-8 secretion by showing that ligation of this molecule on GF, and CD40+ fibroblast subsets in particular, up- regulates secretion of these cytokines in vitro.      

Glycoprotein synthesis in cells infected with vaccinia virus. I. Non-virion glycoproteins

When vaccinia-virus infected HeLa cells were incubated in medium containing radioactively labeled glucosamine, the specific activity of the UDP-N-acetylhexosamine pool increased linearly at a rate similar to that of uninfected cells. Nevertheless, starting at 2 hr after infection, hexosamines were incorporated into glycoproteins at a progressively lower rate. Furthermore, from electrophoretic analysis it appeared as though synthesis of the major glycoproteins of uninfected cells was arrested and new glycoproteins were labeled. After equilibrium centrifugation the major vaccinia-induced glycoproteins did not sediment with infectious virus but a large portion was recovered from fractions rich in cell membranes and containing particulate material. Glycoproteins of similar electrophoretic mobilities were made in vaccinia-infected HeLa and chick cells. Both actinomycin D and cycloheximide inhibited the labeling of all virus-induced glycoproteins whereas rifamycin derivatives had a selective effect.     

'Clock' and 'motor' components in absolute coordination of rhythmic movements

Human subjects swung, through motions at the two wrists, hand-held pendulums of variable mass and length. Within a pair, the two pendulums could be of the same or different magnitude. The subjects were required to produce a coordinated state in which the two rhythmic units oscillated at a single common period. Fifty-four conditions of absolute coordination, that is, 54 different pairs of wrist-pendulum systems, were investigated for each of three subjects in the course of six sessions. Each condition of absolute coordination was conducted in the out of phase mode and at the single most comfortable period. The period variances of the right and left systems in the 162 instances of absolute coordination were analysed according to a method that assumes that a timekeeper function and a motor implementation function contribute independently to the variance in the periodic timing of a rhythmic movement. The major findings were that in absolute coordination: (a) a system's 'motor' variance, but not its 'clock' variance, depended on the deviation of the period of absolute coordination tau from the system's characteristic period; (b) right and left 'clock' variances were related and (c) neither the 'motor' variances nor the 'clock' variances were affected by deviations in the mean phase relation from 180 degrees. The results were discussed in terms of their implications for interpreting von Holst's notions of maintenance tendency and magnetic effect and, more generally, the neural and dynamical basis of absolute coordination.     

Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.      

Pharmacokinetics and tissue disposition of the biological response modifier BAY i 7433 (copovithane) in patients with cancer

Summary Copovithane is an uncharged, water-soluble, synthetic polymer with an average molecular weight of 5800 daltons. It demonstrates antitumor activity in vivo against a variety of tumors in animal models but is inactive in vitro. This agent has been found to have immunorestorative activity in man. In concert with its phase I clinical trial, copovithane concentrations were analyzed by HPLC in plasma, urine, and autopsy and in tumor biopsy specimens obtained from patients. Copovithane was cleared from plasma biphasically with a mean t_1/2 of 11.1±4 min and a t_1/2 of 246±78 min at the dose of 1 g/m², while the plasma half-lives increased to 57.7±12 and 718±149 for the alpha and beta phases, respectively, at the 10 g/m² dose, demonstrating clear, dose-dependent pharmacokinetics. There were no significant differences between dose 1 and dose 4 pharmacokinetics. The apparent volume of distribution (V_d) was 14.5±1. at the 1 g/m² dose and increased to 73 1. at the 33 g/m² dose. The calculated mean clearance rate for copovithane in plasma was between 2.4 and 5.4 mg/kg x min and did not appear to be dose-dependent. The urinary excretion of copovithane was approximately 5% of the administered dose over 120 h at the 1 g/m² dose and decreased to 1% at the 33 g/m² dose. In seven tumor biopsy samples, concentrations of drug in tumor varied from 1- to 1000-fold higher than that found in concurrent plasma samples. In three autopsy samples, the highest concentrations were found in kidney, intestine, and liver, in decreasing order. These studies show that copovithane exhibits dose-dependent changes in pharmacokinetics at doses between 1 and 33 g/m². However, copovithane does penetrate well to tumor tissues, achieving high tumor/plasma ratios. In addition, copovithane concentrations were highest in kidney tissue, which may be a site for potential organ toxicity.     

Infratemporal fossa and lateral skull base dissection: long-term results

In 1981, we described a new surgical technique featuring en bloc removal of infratemporal fossa malignancies. This approach offered a systematic resection of cancers in this region and was designated "stylohamular dissection" because the medial boundary of the bloc is surgical plane between the styloid process and the hamulus of the pterygoid. All structures lateral to this plane are removed, sparing the internal carotid artery. Since 1977, twenty infratemporal fossa and lateral skull base dissections have been performed for palliation of metastatic or recurrent disease in the infratemporal fossa. Most patients obtained palliation of trismus, facial pain, or relief from an unmanageable ulcerating lesion. This technique offers improved average disease-free intervals, as well as enhanced survival rates compared to non-en bloc resections. A summary of the case presentations, survival statistics, and surgical technique with detailed cadaver dissections are presented.